The long term objectives of these investigations is to use stereoisomeric opiate receptor affinity labels to more completely describe the structural and stereochemial requirements of opite agonist receptors. Furthermore, these studies are designed to demonstrate unequivocally whether different opiate agonist receptors possess different binding subsites for structurally dissimilar opiate ligands or if there are distinct opiate agonist receptors having unique structural and stereochemical requirements for non-phenolic ligands. The specific aims of this proposal are to synthesize and pharmacologically evaluate all 4 optical isomer of the novel amine analogues of methadol as selective opiate affinity labels. The compounds will be evaluated using appropriate in vitro and in vivo opiate assay models to determine: (1) if these compounds exhibit covalent (non-equilibrium) binding to opiate receptors; (2) if the chirality of these novel ligands influences the ability of the compounds to form covalent bonds with opiate receptors; (3) whether or not different opiate receptors demonstrate different stereoselectivities toward these ligands; and (4) if these non-phenolic ligands bind to different subsites of a common population of opiate receptors than do phenolic ligands.